Types of Clearly Defined Headache Disorders.
Previously, headache disorders were not clearly distinguished and it was widely believed that they formed part of a continuum and were strongly related. In 1988, The International Headache Society, (IHS) via its ad hoc committee on classification published a document entitled Classification and Diagnostic Criteria for Headache Disorders, Cranial Neuralgias and Facial Pain (Classification and Diagnostic Criteria for Headache Disorders, 1988). A new entity was here defined by name of tension-type headache. This entity was practically the same as conditions previously called tension headache, muscle contraction headache, psycho-myogenic headache and idiopathic headache. The IHS classification also defined a number of other specific headache diseases. Today it therefore gives no meaning to talk about headache in general. It would be the same as to discuss bellyache and chest pain without specifying its type and etiology. Due to the development in diagnostic accuracy research results obtained before 1988 have uncertain validity.
Tension-type headache was subdivided by the IHS Classification Committee into an episodic form occurring less than half of all days and a chronic form occurring half of all days or more. Furthermore, both of these divisions were further subdivided into a form with disorder of pericranial muscle and a form without such disorder. It is thus crucial that research and patents specify which of the subforms are included.
Before the entity of tension-type headache was created, it was widely believed that this kind of headache was caused by muscle ischemia, a concept later disproven by the present inventors nark et al. 1990) The term tension-type headache was created in order to indicate that experts disagreed with the notion of tension-type headache being simply a kind of muscle pain. In fact, the term idiopathic headache was suggested. There is only a moderate co-morbidity with neck pain and low back pain in sufferers of tension-type headache. Furthermore, Electromyography (EMG)-measurements have failed to detect an increase of muscle contraction sufficient to cause pain on a purely mechanical basis in tension-type headache patients whereas central factors such as depression and anxiety have been attributed a significant role. Finally, a genetic factor has recently been shown to be involved in tension-type headache (.O slashed.stergaard et al. 1996). From the point of view of mechanisms and definition tension-type headache is thus a specific entity which may or may not share mechanisms with muscle pain in the head and in other parts of the body. The classification and diagnostic criteria for tension-type headache are shown in Tables I and II.
TABLE I Classification of headache disorders, cranial neuralgias, and facial pain (Headache Classification Committee 1988). 1. Migraine 2. Tension-type headache 3. Cluster headache and chronic paroxysmal hemicrania 4. Miscellaneous headaches unassociated with structural lesion 5. Headache associated with head trauma 6. Headache associated with vascular disorders 7. Headache associated with non-vascular intra-cranial disorder 8. Headache associated with substances or their withdrawal 9. Headache associated with noncephalic infection 10. Headache associated with metabolic disorder 11. Headache or facial pain associated with disorder of cranium, neck, eyes, nose, sinuses, teeth, mouth or other facial or cranial structures 12. Cranial neuralgias, nerve trunk pain and deafferentation pain 13. Headache not classifiable
TABLE II Diagnostic criteria for episodic and chronic tension-type headache (Headache Classification Committee 1988) II.1. Episodic tension-type headache A. At least 10 previous headache episodes fulfilling criteria B-D listed below. Number of days with such headache &lt;180/year (&lt;15/month) B. Headache lasting from 30 minutes to 7 days C. At least 2 of the following pain characteristics: 1. Pressing/tightening quality 2. Mild or moderate severity (may inhibit, but does not prohibit activities) 3. Bilateral location 4. No aggravation by walking stairs or similar routine physical activity D. Both of the following: 1. No nausea or vomiting (anorexia may occur) 2. Photophobia and phonophobia are absent, or one but not the other is present E. At least one of the following: 1. History, physical and neurological examinations do not suggest one of the disorders listed in groups 5-11 2. History and/or physical and/or neurological examinations do suggest such disorders, but they are ruled out by appropriate investigations 3. Such disorders are present, but tension-type headache does not occur for the first time in close temporal relation to the disorder II.2. Chronic tension-type headache A. Average headache frequency 15 days/month (180 days/year) for 6 months fulfilling criteria B-D listed below B. At least 2 of the following pain characteristics: 1. Pressing/tightening quality 2. Mild or moderate severity (may inhibit, but does not prohibit activities) 3. Bilateral location 4. No aggravation by walking stairs or similar routine physical activity C. Both of the following: 1. No vomiting 2. No more than one of the following: Nausea, photophobia or phonophobia D. At least one of the following: 1. History, physical and neurological examinations do not suggest one of the disorders listed in groups 5-11 2. History and/or physical and/or neurological examinations do suggest such disorders, but they are ruled out by appropriate investigations 3. Such disorders are present, but tension-type headache does not occur for the first time in close temporal relation to the disorder
Epidemiological studies done by the inventors have shown that chronic tension-type headache affects three percent of the population at any given time, the lifetime prevalence being as high as six percent (Rasmussen et al. 1991). Severe episodic tension-type headache defined as persons having headache twice a week or more occurs in approximately ten percent of the population. Thus, tension-type headache is a serious problem with significant socio-economic implications, involving enormous loss of workdays and quality of life.
Previous Findings in General Pain Physiology and Pain Pharmacology
The possible pathogenic mechanisms of tension-type headache have previously been studied and discussed by Langemark et al. (Langemark et al. 1987, 1988, 1989) and by the group of Jean Schoenen (Schoenen et al. 1987, 1991a, b). The latter group have mainly focused on electrophysiological recordings as electromyography, and the jaw opening reflex as reflected by the so-called exteroceptive silent period (ES2) (Schoenen et al. 1987). On the basis of shortened ES2 periods in patients with chronic tension-type headache compared to healthy controls a limbic dysfunction was suggested, but these results have later been disproven by more systematic investigations (Bendtsen et al. 1996a, Lipchik et al 1996, Zwart and Sand, 1996). Schoenen and other groups have also studied mechanical pain thresholds on the extremities as well as in the cranial region and decreased mechanical pain thresholds in severely affected patients with chronic tension-type headache were reported (Schoenen et al. 1991a, Langemark et al. 1989), whereas patients with the episodic form of tension-type headache are reported to have normal thresholds compared to healthy controls (Hatch et al. 1992, Goebel et al. 1992, Jensen et al. 1993b). These authors suggested that central mechanisms may be involved in the chronic subform and that the peripheral mechanisms played a role in the episodic form, but provided no further clues or arguments about the underlying mechanisms. One more recent congress presentation and two scientific papers by the present inventors have focused on the sensory mechanisms in tension-type headache as decreased thresholds and tolerances were found in and outside the head of patients with chronic tension-type headache indicating a generally increased sensitivity to noxious and innocuous stimuli (Bendtsen et al. 1995b, 1996b and 1996c). Similarly a congress report and a scientific paper present data from patients studied during and outside a spontaneous tension-type headache episode (Jensen et al. 1995a and 1995b). Muscle tenderness was increased during the headache episode, whereas mechanical pain thresholds remained unchanged and thermal pain tolerance decreased. It was concluded that a peripheral sensitization may be one of the primary sources of pain and that central sensitization may contribute to and maintain the pain in chronic tension-type headache. However, these data did not provide any further clues for more specific localizations of the sensitization, could not lead to a precise experimental model and finally did not lead to guidance for specific treatment of tension-type headache.
Peripheral Induction of Central Sensitization
One of the most exciting developments in pain research over the past decades has been the recognition that the response generated by the somatosensory system to a defined input is not fixed or static. In particular, the increased knowledge on central sensitization, i.e. increased excitability of neurons in the central nervous system, has been a major breakthrough in the understanding of chronic pain. In 1983 Woolf and colleagues (Woolf 1983) demonstrated for the first time that a prolonged noxious input from the periphery is capable of sensitizing spinal dorsal horn neurons. It has later been demonstrated that the central sensitization is induced by repetitive C-fibre, but not A-fibre, input (Yaksh and Malmberg 1994). In the sensitized state, a low-intensity stimulus can generate pain, the phenomenon of allodynia. The low-intensity stimulus is mediated via low-threshold afferents, A-b-fibres, which do not normally mediate pain, and it has been. suggested that the major cause of increased pain sensitivity in the chronic pain condition is an abnormal response to A-b-sensory input (Woolf and Doubell 1994). The original findings by Woolf and colleagues on spinal dorsal horn sensitization have later been confirmed by numerous independent laboratories (Mense 1993), and a similar sensitization of trigeminal brainstem nociceptive neurons following stimulation of craniofacial muscle afferents has been reported by Hu et al. (Hu et al. 1992). While central sensitization may be of relevance in many different chronic pain conditions it is particular likely in muscle pain, because input from muscle nociceptors is more effective in inducing prolonged changes in the behavior of dorsal horn neurons than is input from cutaneous nociceptors (Wall and Woolf 1984).